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Transplantation Proceedings 09/2000; 32(5):1005. · 1.00 Impact Factor
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D Mital,
Z Guo,
Y Tian,
J Shen,
W Podlasek,
P Foster,
H Sankary,
S Jensik,
L McChesney,
A Chong,
B Olack, J Williams
Transplantation Proceedings 03/1998; 30(2):515. · 1.00 Impact Factor
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ABSTRACT: The inability to provide an adequate supply of human organs for clinical transplantation has created a strong interest in the use of nonhuman, especially nonprimate, organs. The first biological obstacle confronting such discordant transplantations is a series of violent reactions that result in hyperacute rejection of the xenograft. Significant advances in controlling hyperacute rejection have been achieved recently through the generation of transgenic pig donors bearing human complement regulatory proteins. However, when hyperacute rejection is averted, the xenografts are rejected in 2-70 days in spite of high-dose immunosuppression, by a process collectively termed delayed xenograft rejection. Delayed xenograft rejection is characterized by a refractoriness to conventional immunosuppression, extensive xenoreactive antibody deposition, and cellular infiltration that is dominated by macrophages. We have examined the features of extended host and graft response in the concordant hamster-to-rat xenotransplant model, where such features have historically been obscured by early graft destruction. Hamster hearts transplanted into rats do not encounter hyperacute rejection but are rejected within 3-4 days when xenoreactive antibody titers rise exponentially to levels that elicit a classical antibody- and complement-mediated acute xenograft rejection. We have successfully blocked acute xenograft rejection by a combination of immunosuppressive agents, leflunomide, and cyclosporine. Stopping the immunosuppression resulted in graft rejection that is histologically characterized by extensive xenoreactive antibody deposition and cellular infiltration that is predominantly composed of macrophages. We have noted the similarities between the histopathology of rejection of long-surviving concordant xenografts and that described for discordant xenografts and refer to the process of rejection of concordant grafts that have escaped acute xenograft rejection, delayed xenograft rejection.
Transplantation 08/1996; 62(1):90-6. · 4.00 Impact Factor
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ABSTRACT: Preservation-reperfusion injury of hepatic allografts is thought to be associated with Kupffer cell activation and TNF release from the transplanted organ. Confirmation that the allograft is the source of this TNF in an in vivo model is difficult because of rapid equilibration of this cytokine into all compartments. A novel experimental design was devised to aid in accurate localization of the site of TNF release following a orthotopic liver transplant (OLT). In the first group (anhepatic), livers were removed from rats and splanchnic and systemic venous returns were then reestablished using a conduit of donor IVC and portal vein with a portasystemic shunt. In the second group (asplanchnic), the liver, stomach, pancreas, and intestine of the recipient were removed and a donor liver was reimplanted using the recipient IVC as the source of portal blood. The third (OLT-16) and fourth (OLT 8) groups underwent standard OLT with preservation times of 16 and 8 hr in 4 degrees C Euro-Collins solution, respectively. TNF levels were significantly increased in the OLT-16 group compared with the OLT-8 group. There were modest elevations of TNF in the anhepatic model, but the TNF in the asplanchnic model approached baseline. Absence of TNF in the asplanchnic group and a rise in TNF levels in the anhepatic group to that not significantly different from OLT-16 or OLT-8 suggest that a major source of TNF following preservation reperfusion may be the intestine.
Transplantation 05/1996; 61(8):1142-7. · 4.00 Impact Factor
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ABSTRACT: We evaluated the feasibility of using a metallic stented portal vein as a conduit for portacaval shunt in pigs.
A metallic self-expanding stent was placed in the portal vein of five pigs under combined ultrasound and fluoroscopic guidance via a percutaneous transhepatic approach. After 6 weeks, a portacaval shunt was performed using the stented portal vein as a conduit. A single angiogram followed immediately by sacrifice and histologic examination was performed on each pig at a varying time interval postshunt.
One pig died 3 days after the shunt procedure because of a presumed surgical technical failure and a consequent thrombosed portal vein. Angiographic patency of the portacaval shunt was confirmed in the four remaining pigs. Postmortem histologic evaluation showed more complete endothelialization and subintimal organization in the more chronic stents. Thrombus occurred only in the stent of the pig that died. There was no significant luminal obstruction in the other four stents.
Our results suggest that a stented portal vein can be used successfully as a conduit for portacaval shunt in pigs.
Academic Radiology 05/1996; 3(4):325-9. · 1.69 Impact Factor
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ABSTRACT: Data from recent studies suggest that donor fasting imparts a beneficial effect on the viability of transplanted hepatic allografts. Because starvation may temporarily inactivate Kupffer cells, and because these cells are the likely mediators of liver injury after prolonged preservation-reperfusion, the purpose of this study is to establish a link between improved organ viability and Kupffer cell inactivation caused by donor allograft fasting. In an in vivo rat liver transplant model, 48 hours of donor fasting (1) improved allograft viability, (2) significantly decreased Kupffer cell phagocytosis, and (3) significantly decreased cytokine (tumor necrosis factor [TNF]) production postrevascularization. These data validate work from previous studies demonstrating that donor fasting improves allograft viability and furthermore support our previous research implicating activation of Kupffer cells as a causative agent of cold ischemia-preservation injury.
Hepatology 11/1995; 22(4 Pt 1):1236-42. · 11.66 Impact Factor
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ABSTRACT: Despite improvements in preservation solutions, hepatic allografts continue to be lost from primary nonfunction. Previous work by this group and others has established that donor fasting improves the viability of hepatic allografts. We have also established an association between viability of stored organs and serum TNF levels. The purpose of this study was to determine whether improved viability of hepatic allografts from fasted donors is associated with lower peripheral serum TNF levels. TNF was measured using a bioassay employing a WEHI cell line. Transplanted livers from fasted donors displayed gross deglycogenation had less bile flow postrevascularization and increased postoperative AST, but had significant improvement in viability and were associated with significantly less TNF recovered from the peripheral circulation. The association of improved viability and diminished serum TNF and previous work that links changes in postrevascularization TNF levels with changes in Kupffer cell activity suggest a possible cause for improved survival of recipients of fasted allografts.
Journal of Surgical Research 04/1995; 58(3):337-43. · 2.25 Impact Factor
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ABSTRACT: Nonanastomotic strictures after liver transplantations are a source of significant morbidity, often necessitating retransplantation. The purpose of this study was twofold: first to identify features associated with the development of this lesion; second, to make technical modifications that will decrease the incidence of this problem. In the first part of this study, 15 of 131 patients were diagnosed with nonanastomotic biliary stricture. A stepwise logistic-regression analysis associated donor cold ischemic time and dopamine dose with the development of nonanastomotic biliary strictures. All these patients had arterial reconstruction after partial revascularization of the liver with portal venous blood. Because the bile duct receives its blood supply from only the hepatic artery, we hypothesized that the prolonged period of warm ischemia from staged reconstruction of the vascular supply would promote the development of this lesion. In a second part of this study, the stricture rate in 45 patients with simultaneous revascularization using both the hepatic artery and portal vein was compared with that in 83 patients from the first part of this study initially revascularized with portal venous blood. All patients in the second study had grafts preserved using UW solution. Only 1 patient with simultaneous revascularization developed a nonanastomotic biliary stricture. Because we were unable to identify any significant complications related to this method of revascularization, we propose that the hepatic artery and portal vein should be released simultaneously, especially in patients receiving a graft with prolonged storage time.
Hepatology 02/1995; 21(1):63-9. · 11.66 Impact Factor
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Transplantation Proceedings 05/1993; 25(2):1964-7. · 1.00 Impact Factor
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Transplantation Proceedings 03/1993; 25(1 Pt 2):928-30. · 1.00 Impact Factor
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Transplantation 08/1992; 54(1):170-2. · 4.00 Impact Factor
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ABSTRACT: Between August 1985 and December 1990, 198 liver transplantations were performed. Among 18 patients, 20 biliary strictures were identified, which were categorized as anastomotic (n = 6), nonanastomotic central hilar (n = 8), and nonanastomotic peripheral (n = 6). Pretransplant disease, hepatic artery patency, presence of acute or chronic rejection, and donor cold ischemia times were tabulated for each case. Among the six patients with peripheral strictures, three had sclerosing cholangitis prior to transplantation. Three patients with nonanastomotic strictures experienced chronic rejection. The mean cold ischemia time for patients with nonanastomotic strictures was 9.75 hours versus 8.1 hours for nonstrictured transplants (P = .025). Balloon dilation was performed in 13 patients; follow-up longer than 6 months was available for nine patients. Dilation was successful in four cases. Among the five failures, only one patient has needed surgery. An association was noted between nonanastomotic biliary strictures and prolonged donor cold ischemia time, between peripheral nonanastomotic strictures and pretransplant sclerosing cholangitis, and between nonanastomotic strictures and chronic rejection. Percutaneous balloon dilation was found useful in the treatment of the strictured transplant.
Journal of Vascular and Interventional Radiology 12/1991; 2(4):533-8. · 2.08 Impact Factor
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ABSTRACT: Changes in the qualitative character of the portal tract infiltrate of hepatic allografts can influence the diagnosis of acute rejection. Since qualitative data rely on subjective findings, the aim of this study was to perform a quantitative analysis of portal tract infiltrates to improve the accuracy of the diagnosis of acute rejection. A total of 431 serial hepatic biopsies in 58 consecutive adult patients were obtained. The average number of eosinophils, neutrophils, and lymphocytes in each portal tract were counted. The area of each portal tract was determined using an optical micrometer. Rejection was confirmed by an independent investigator using both clinical and histologic criteria. Using a backward stepwise logistic regression analysis, we found that eosinophils were the only variable predictive of rejection. Using this model, the probability of having rejection on a single biopsy can be determined with greater than 90% accuracy.
The American Journal of Surgery 02/1991; 161(1):131-4; discussion 134-5. · 2.78 Impact Factor
